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Impact of Pulmonary Rehabilitation on Exercise Tolerance and Quality of Life in Patients With Idiopathic Pulmonary Fibrosis: A SYSTEMATIC REVIEW AND META-ANALYSIS

Gomes-Neto, Mansueto, PT, PhD; Silva, Cassio Magalhães, PT, Msc; Ezequiel, Diego, PT; Conceição, Cristiano Sena, PT, PhD; Saquetto, Micheli, PT, MSc; Machado, Adelmir Souza, MD, PhD

Journal of Cardiopulmonary Rehabilitation and Prevention: September 2018 - Volume 38 - Issue 5 - p 273–278
doi: 10.1097/HCR.0000000000000273
Scientific Review

Background: Patients with pulmonary fibrosis are living longer and present with an increasing number of comorbidities over time. Pulmonary rehabilitation, as a nonpharmacological approach, may be promising in these patients, although there is limited information on the impact of pulmonary rehabilitation on exercise tolerance and quality of life. Thus, conducting a systematic review and meta-analysis, the purpose of this study was to determine the effects of pulmonary rehabilitation on exercise tolerance and quality of life in patients with idiopathic pulmonary fibrosis.

Methods: We searched MEDLINE, Cochrane Library, Embase, Scielo, PEDro, and CINAHL (from the earliest date available to June 2016) for trials. Study selection included randomized controlled trials (RCTs) that examined the effects of pulmonary rehabilitation in patients with idiopathic pulmonary fibrosis. Two reviewers selected studies independently. Data were extracted from published RCTs. Study quality was evaluated using the PEDro scale. Weighted mean differences, standard mean differences, and 95% CIs were calculated.

Results: We analyzed data from 5 RCTs comparing a pulmonary rehabilitation group with a control group. Pulmonary rehabilitation improved exercise tolerance weighted mean differences (44 m; 95% CI, 5.3-82.8) compared with no exercise. The meta-analyses also showed significant improvement in symptoms, impact, and total score from the St George's Respiratory Questionnaire for participants in pulmonary rehabilitation compared with control. No serious adverse events were reported.

Conclusion: Pulmonary rehabilitation is effective in increasing exercise tolerance and improving quality of life in patients with idiopathic pulmonary fibrosis.

We performed a systematic review and meta-analysis to investigate the effects pulmonary rehabilitation on exercise tolerance and quality of life in patients with idiopathic pulmonary fibrosis. Pulmonary rehabilitation is effective in increasing exercise tolerance and improving quality of life in these patients.

Department of Physical Therapy (Drs Gomes-Neto and Conceição and Messrs Silva and Saquetto) and Department of Biomorphology (Dr Machado), Federal University of Bahia, Salvador, Brazil; and Department of Physical Therapy (Mr Ezequiel), Hélio Rocha, Salvador, Brazil.

Correspondence: Mansueto Gomes-Neto, PT, PhD, Universidade Federal da Bahia—UFBA, Av. Reitor Miguel Calmon s/n, Vale do Canela, Salvador, CEP 40.110-100, Brazil (mansueto.neto@ufba.br).

All authors have read and approved the article.

The authors declare no conflicts of interest.

Idiopathic pulmonary fibrosis is a progressive fibrosing parenchymal lung disease, causing progressive worsening of dyspnea and lung function, fatigue, reduced exercise tolerance, and diminished health-related quality of life with few therapeutic options.1 , 2 The declines in pulmonary function and exercise tolerance are the important manifestations of idiopathic pulmonary fibrosis.3 , 4 Because patients with idiopathic pulmonary fibrosis have a limited response to conventional pharmacological treatment, pulmonary rehabilitation (PR) as a nonpharmacological approach may be promising in these patients.5 PR is an evidence-based standard of care for patients with pulmonary diseases.6 , 7 Therefore, PR may be of added value for stable patients in an attempt to improve their ability to cope with daily living. PR has also been accepted among the nonpharmacological treatment options as a means to reduce dyspnea and improve exercise tolerance in patients with pulmonary fibrosis.8 , 9

According to the most recent American Thoracic Society and the European Respiratory Society guidelines, PR has only a “weak” level of recommendation for patients with pulmonary fibrosis.10 However, there is no doubt that PR can be beneficial in some patients with idiopathic pulmonary fibrosis.11 Meta-analysis techniques have not previously been used to investigate the effects of PR in patients with idiopathic pulmonary fibrosis. This technique minimizes subjectivity by standardizing treatment effects of relevant studies into effect sizes, pooling the data, and analyzing these data to draw conclusions. The aim of this systematic review and meta-analysis was to analyze data from published randomized controlled trials (RCTs) that have investigated the effects of PR on exercise tolerance and quality of life in patients with idiopathic pulmonary fibrosis.

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METHODS

This meta-analysis was completed in accordance with PRISMA guidelines.12

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ELIGIBILITY CRITERIA

This systematic review included all RCTs that studied the effects of PR in patients with idiopathic pulmonary fibrosis. To be eligible, each trial should have randomized idiopathic pulmonary fibrosis patients to at least 1 group of PR, with comparison to controls. PR was defined as a comprehensive, multidisciplinary program composed of a combination of exercise training, education, and behavior modification techniques. The outcomes of interest were exercise tolerance and quality of life.

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INFORMATION SOURCES AND SEARCH

We searched for studies on PEDro, CINAHL, MEDLINE, and the Cochrane Library up to June 2016. A search strategy was developed, and whenever possible, controlled vocabulary was used. To sensitize the search, key words and their synonyms were used. The search strategy included 4 groups of keywords: study design, participants, interventions, and outcome measures. In PubMed/MEDLINE, an optimally sensitive search strategy was used to identify RCTs.13 References of the articles included in this systematic review were reviewed to identify other potentially eligible studies.

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DATA COLLECTION AND ANALYSIS

A search strategy was used to obtain titles and abstracts of studies that might be relevant for this review. Each abstract identified in the search was independently evaluated by 2 authors. If at least 1 of the authors considered 1 reference eligible, the full text was assessment. Two reviewers evaluated the full-text articles for eligibility.

Two authors independently extracted data from the published reports using standard data extraction forms adapted from The Cochrane Collaboration's13 model. Aspects of the study population, types of intervention performed, follow-up and loss to follow-up, outcome measures, and results were reviewed. Disagreements were resolved by 1 of the authors. Any further information required from the original author was requested by e-mail.

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QUALITY OF META-ANALYSIS EVIDENCE

The PEDro scale is a useful tool for assessing the methodological quality of physiotherapy and rehabilitation RCTs.14 In this review, quality of the methodology was scored on the PEDro scale on the basis of a Delphi list15 by 2 authors. The score range is 0 to 10.16

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DATA SYNTHESIS AND ANALYSIS

Pooled effect estimates were obtained by comparing the least square mean percentage change from baseline to the end of the study for each group, and were expressed as the weighted mean difference between groups. When the SD of change was not available, the SD of the baseline measure was used for the meta-analysis. Calculations were made using a fixed and random-effects model and one comparison was made: PR versus control group. An α value of .05 was considered significant. Statistical heterogeneity of the treatment effect among studies was assessed using Cochran's Q-test and the inconsistency I 2 test, in which values above 25% and 50% were considered indicative of moderate and high heterogeneity, respectively.17 All analyses were conducted using Review Manager, version 5.3 (The Cochrane Collaboration).18

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RESULTS

DESCRIPTION OF SELECTED STUDIES

The initial search led to the identification of 56 abstracts, 8 of which were considered potentially relevant and were retrieved for detailed analysis. Five studies met the eligibility criteria. Figure 1 shows the PRISMA flow diagram of studies in this review.

Figure 1

Figure 1

These 5 articles19–23 were fully analyzed, approved by both reviewers, and had their data extracted. Each of the articles was scored using the PEDro scale methodology by both reviewers. Studies included in this review had PEDro scores of 3 to 7, and the mean methodological quality of the included studies was 6.1. The results of the assessment of the PEDro scale are presented individually in Table 1.

Table 1

Table 1

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STUDY CHARACTERISTICS

The number of participants in the included studies ranged from 2120 , 22 to 32.19 , 21 The mean age of the participants ranged from 66 to 68 years. All of the studies included patients of both genders, but there was an overall predominance of male participants. Table 2 summarizes the PR characteristics of the included trials.

Table 2

Table 2

The parameters used in the application of PR were reported in most studies. In all, 10 to 12 weeks of PR programs were performed. Furthermore, sessions were performed 2 times per week. The PR program included aerobic, resistance, and flexibility exercise modes in all studies. The characteristics of the PR programs included are provided in Table 3.

Table 3

Table 3

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EFFECT OF PR ON EXERCISE TOLERANCE

Four studies assessed exercise tolerance as an outcome.19–21 , 23 The meta-analyses showed significant improvement in exercise tolerance of 44 m (95% CI, 5.3-82.8; n = 113) for 6-minute walk distance (6MWD) for patients in the PR group compared with the control group (Figure 2).

Figure 2

Figure 2

Four studies assessed quality of life.19–21 , 23 In all studies the quality of life was assessed using the St George's Respiratory Questionnaire although Gaunaurd et al22 only used the Symptoms dimension. A total of 113 patients were included in these 4 studies. In the study by Vainshelboim et al,21 quality of life showed a between-group difference in 2 dimensions (Symptoms and Impact) and in total score, whereas Gaunaurd et al22 showed a between-group difference in the Symptoms dimension in favor of PR. Meta-analyses showed significant improvement in Symptoms score, Impact score, and total score for participants in the PR group compared with the control group (Figure 3). A nonsignificant difference in activity score was found for participants in the PR group compared with the control group.

Figure 3

Figure 3

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DISCUSSION

The main results of our systematic review indicated that PR is effective in increasing exercise tolerance and improving quality of life in patients with idiopathic pulmonary fibrosis. These findings highlight the importance of PR as part of the treatment of patients with idiopathic pulmonary fibrosis.

This systematic review with meta-analysis is important because it analyzes PR as a potential coadjutant modality in the treatment of patients with idiopathic pulmonary fibrosis. A decreased level of exercise tolerance is important because it has been associated with an increased risk of mortality.24 , 25 Lower 6MWD is strongly and independently associated with an increased mortality rate for patients with idiopathic pulmonary fibrosis. In addition, 6MWD is a better predictor of death at 6 months than is forced vital capacity.26 , 27

Our systematic review showed that PR is effective in increasing exercise tolerance. In our meta-analysis, the mean of 6MWD in the analyzed studies was 422 m at baseline compared with 451 m at the end of the intervention. Specifically, the weighted mean difference in 6MWD was 44 m favoring PR, which represents an improvement of 11%. A minimal clinically important difference for walk distance in patients with idiopathic pulmonary fibrosis is not available.

In addition, improvement of quality of life is clearly important for patients with idiopathic pulmonary fibrosis, because both physical health and level of independence are negatively impacted by the disease. In all studies, the quality of life was assessed using the St George's Respiratory Questionnaire. The St George's Respiratory Questionnaire has been used in idiopathic pulmonary fibrosis studies and its psychometric properties reviewed in 30 studies to date.28 Our meta-analysis showed additional improvement in Symptoms, Impact, and total score for patients in the PR group compared with the control group.

PR has also been shown to have positive effects on exercise tolerance, activities of daily life, and quality of life in the context of other pulmonary chronic diseases.29–31 Thus, PR as a nonpharmacological approach may also be promising in patients with idiopathic pulmonary fibrosis. However, before starting an exercise training program, an exercise assessment is needed to individualize the exercise prescription, evaluate the potential need for supplemental oxygen, identify cardiovascular comorbidities, and help ensure the safety of the intervention.7

The general principles of exercise training in individuals with chronic respiratory disease are no different from those for healthy individuals. The frequency, intensity, and duration are specific to the type of activity and should be tailored to the patient's ability to safely perform the activity. Although the optimal intensity cannot be defined on the basis of available information, much of the exercise that is associated with good health in published reports is at least of moderate intensity.7 , 32

The duration of programs ranged from 10 to 12 weeks. Studies show that benefits of PR appear to diminish over 6 to 12 months, with quality of life better maintained than exercise capacity.33 , 34 The maximum duration of the intervention in the included studies was 12 weeks. Thus, the long-term effects of PR remain unclear.

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STUDY LIMITATIONS

Given the small pool of available studies, some caution is warranted when interpreting our results. A notable limitation of the included studies is the small sample sizes in the studies. Further investigation is required to explore how the positive effects of respiratory muscle training can be sustained over time, as well as to determine optimum dosages, duration, and the outcomes when used in combination with peripheral muscle training. Clearly, the value of PR in the survival of patients with idiopathic pulmonary fibrosis deserves special attention in future studies. Research in the field of PR in people with idiopathic pulmonary fibrosis should be focused on providing indications regarding evidence-based standards for exercise prescription and on careful clinical evaluation and exercise-related risk assessment. Further research, including evaluation of the relative impact of standard multidisciplinary PR on exercise tolerance and quality of life compared with exercise training alone is warranted.

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CONCLUSION

Taking into account the available studies, this systematic review with meta-analysis showed that PR is effective in increasing exercise tolerance and quality of life in patients with idiopathic pulmonary fibrosis. More well-designed RCTs are necessary to determine the most appropriate methods (intensity, frequency, and duration) to optimally tailor the PR to the particular characteristics of a patient subgroup or individually.

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Keywords:

exercise; idiopathic pulmonary fibrosis; quality of life

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